Sensor and Method for Removing Interfering Substance

ABSTRACT

A technique is provided, wherein any influence, which would be otherwise exerted on a reaction of an objective substance caused by a reagent enzyme by an interfering substance contained in a specimen, is suppressed in relation to an electrochemical sensor for measuring the objective substance contained in the specimen. A sensor comprises a substrate; a detecting unit which is provided on the substrate and which detects an objective substance; a filter which covers the detecting unit, which permits permeation of the objective substance on one hand, and which regulates permeation of an interfering substance contained in a sample on the other hand; and removing unit which removes the interfering substance adhered to the filter.

TECHNICAL FIELD

The present invention relates to a sensor for measuring an objectivesubstance contained in a sample, and a method for removing aninterfering substance adhered to the sensor.

BACKGROUND ART

An electrochemical sensor is known, for example, as a sensor formeasuring an objective substance (specified component) contained in asample. The electrochemical sensor is the sensor which is capable ofdetecting a minute amount of current by utilizing an electrochemicalreaction. In the case of a glucose sensor of the subcutaneous retentiontype (to be retained subcutaneously beneath the skin), when glucosemolecules, which exist in a specimen or sample, arrive at the enzymedeveloped on an electrode, glucose is oxidized in accordance with theenzymatic reaction. It is possible to estimate the concentration ofglucose in a body fluid on the basis of a response current signalobtained by electrochemically oxidizing hydrogen peroxide (H₂O₂) whichis produced during this process. The sample is exemplified, for example,by an intercellular fluid which exists extracellularly in thesubcutaneous tissue. The method, in which the response current obtainedby allowing glucose contained in a sample to react together with areagent enzyme (for example, glucose oxidase (GOD), glucosedehydrogenase (GDH) or the like) provided on a measuring sensor asdescribed above, is referred to as “enzyme electrode method”. Further, asensor is also known, which adopts such an optical detecting method(referred to as “colorimetric method” in some cases) that the intensityis measured at a color developing wavelength while previously applying acolor developing reagent enzyme (for example, hexokinase (HK) or thelike) which specifically causes a reaction of an objective substancecontained in a sample.

In this specification, a part or region, which is provided on asubstrate of a measuring sensor and which is provided to detect anobjective substance contained in a sample, is referred to as “detectingunit”. For example, the reaction reagent is retained in the detectingunit. The body fluid contains, for example, microorganisms (for example,bacteria and fungi), protein, fibrin, and lipid in addition to glucoseas the objective substance. For example, when the microorganism existsaround the detecting unit (for example, an electrode of a glucosesensor), it is feared that the measurement accuracy may be deterioratedby destroying the enzyme developed on the electrode and/or consuming,for example, glucose, oxygen or the like. In relation thereto, such atechnique has been suggested that an antifungal agent, an antibiotic orthe like is previously mixed with the enzyme (see, for example, PatentDocument 1).

On the other hand, if the subcutaneous retention period is prolonged,then protein, fibrin and the like gradually adhere to the electrode, andthe formation of foreign body capsule (FBC) is induced. Finally, maturedFBC such as vascular fibrous tissue is formed (see, for example,Non-Patent Document 1). If such a situation arises, for example, glucosehardly arrives at the electrode. It is feared that any influence may beexerted on the measurement of the glucose concentration. In relationthereto, a biosensor has been also suggested, comprising a first filmwhich is a porous film for covering an electrode and which has anelectron donor region formed on a surface thereof for allowing proteinand fibrin to easily adhere, and a second film which is combined withthe electron donor region of the first film and which has a bondinghydrogen atom donor composed of phenyl ring (see, for example, PatentDocument 2).

PRECEDING TECHNICAL DOCUMENTS Patent Documents: Patent Document 1:JP2003-513230A Patent Document 2: JP11-513914A Non-Patent Document:

-   Non-Patent Document 1: Inflammation and Biomaterials in Greco R S,    ed. Implantation Biology: the Host Response and Biomedical Devices,    pp 68-80, CRC Press (1994).

SUMMARY OF THE INVENTION Task to be Solved by the Invention

The substance, which includes, for example, the microorganism, protein,fibrin, and lipid as described above, is the interfering substance whichinterferes in (exerts any influence on) the reaction of the objectivesubstance caused by the enzyme on the glucose sensor. It is consideredthat the effect may be lowered as the time elapses, even when anycountermeasure is adopted, for example, such that an agent such as anantifungal agent, an antibiotic or the like is previously mixed with theenzyme and/or an agent is retained by a film for covering the enzyme inorder not to allow the interfering substance to adhere to the enzyme,wherein there is room for improvement.

The present invention has been made taking the forgoing actualcircumstances into consideration, an object of which is to provide sucha technique that any harmful influence is suppressed, which would beotherwise exerted on the detection of an objective substance in adetecting unit by an interfering substance contained in a sample, inrelation to a sensor for measuring the objective substance contained inthe sample.

Solution for the Task

In order to solve the problem as described above, the present inventionadopts the following means. That is, the present invention resides in asensor for measuring an objective substance contained in a sample; thesensor comprising a substrate; a detecting unit which is provided on thesubstrate and which detects the objective substance; a filter whichcovers the detecting unit, which permits permeation of the objectivesubstance on one hand, and which regulates permeation of an interferingsubstance contained in the sample on the other hand; and a removing unitwhich removes the interfering substance adhered to the filter. Thesensor according to the present invention may be, for example, anelectrochemical sensor provided with the detecting unit including areagent enzyme retained on an electrode provided on the substrate. Theinterfering substance, which is referred to in the present invention, isthe substance which interferes in (exerts any influence on) thedetection of the objective substance performed by the detecting unit.For example, when the reagent enzyme, which causes the reaction of theobjective substance, is retained in the detecting unit, any substance orthe like, which interferes in the reaction of the objective substancecaused by the reagent enzyme, can be exemplified as the interferingsubstance.

According to the present invention, the interfering substance is nottransmitted (permeated) through the filter. Therefore, the interferingsubstance does not arrive at the detecting unit. For example, when thesubcutaneous retention period lasts for a long period of time, theinterfering substance, which is contained in the sample, is graduallyadhered and accumulated (deposited) on the filter. If the adhesionamount (accumulation amount) of the interfering substance is excessivelyincreased on the filter, for example, the filter is completely cloggedup. As a result, any smooth arrival of the objective substance at thedetecting unit (including, for example, the reagent enzyme retained onthe detecting unit) is inhibited.

On the contrary, in the present invention, the interfering substance,which adheres to the surface of the filter, can be removed from thefilter in a state in which the filter is exposed to the sample. Forexample, the process for removing the interfering substance as describedabove is executed at every certain periods or on the basis of themonitoring result of the response current signal generated by anelectrochemical sensor when the sensor according to the presentinvention is the electrochemical sensor. Thus, it is possible tosuppress any excessive increase in the adhesion amount of theinterfering substance adhered to the filter. In other words, theinterfering substance can be removed before the adhesion amount of theinterfering substance is excessively increased. Therefore, according tothe present invention, it is possible to suppress any harmful influencewhich would be otherwise exerted by the interfering substance containedin the sample on the detection of the objective substance performed bythe detecting unit. Accordingly, it is also possible to suppress thedeterioration of the measurement accuracy of the objective substance tobe measured by the sensor.

The removing unit, which is provided for the sensor of the presentinvention, may remove the interfering substance adhered to the filter byvibrating the filter. In this case, for example, the removing unit maybe constructed to include a piezoelectric element which is vibrated byapplying a voltage; and vibration transmitting unit which is fixed tothe piezoelectric element and which transmits vibrational energy of thepiezoelectric element to the filter. Accordingly, the interferingsubstance, which adheres to the filter, can be appropriately removedfrom the filter.

The removing unit, which is provided for the sensor of the presentinvention, may remove the interfering substance adhered to the filter bysupplying, to the filter, an agent for decomposing the interferingsubstance. In this case, for example, the removing unit may beconstructed to include a piezoelectric element which is vibrated byapplying a voltage; an accommodating case which accommodates the agent;and a discharge hole which is formed to be open on the accommodatingcase; and the agent may be discharged from the discharge hole bytransmitting vibrational energy of the piezoelectric element to theaccommodating case so that the agent is supplied to the filter. In thisarrangement, when the piezoelectric element is vibrated, the vibrationalenergy is transmitted to the accommodating case, and thus the agent,which is accommodated in the accommodating case, is discharged form thedischarge hole to the filter. Accordingly, the interfering substance,which adheres to the filter, can be appropriately removed from thefilter.

The removing unit, which is provided for the sensor of the presentinvention, may be constructed to have at least a pair of removingelectrodes which are arranged in mutual contact with the filter orclosely to the filter; and the interfering substance adhered to thefilter may be removed by means of electrolytic cleaning for the removingelectrodes performed by applying a voltage between the removingelectrodes. Accordingly, the interfering substance, which adheres to thefilter, can be appropriately removed from the filter. In this case, theremoving electrodes may be arranged so that the interfering substance,which adheres to the removing electrodes and the filter, is formed whilebeing joined or linked together.

In the sensor according to the present invention as described above, thedetecting unit may be used while being retained subcutaneously.

In order to solve the problem as described above, the present inventioncan be also grasped from an aspect of a method for removing theinterfering substance. In particular, the present invention resides in amethod for removing an interfering substance, to be applied to a sensorcomprising a detecting unit which is provided on a substrate and whichdetects an objective substance contained in a sample; the methodcomprising allowing the interfering substance to adhere to a filterbeforehand by covering the detecting unit with the filter which permitspermeation of the objective substance on one hand and which regulatespermeation of the interfering substance contained in the sample on theother hand, and removing the interfering substance adhered to the filterby means of removing unit which removes the interfering substance.According to this removing method, the interfering substance, whichadheres to the filter, can be appropriately removed from the filter.

The foregoing method for removing the interfering substance according tothe present invention can be applied to any one of the sensors asdescribed above. Further, the means for solving the problem according tothe present invention can be combined with each other as far aspossible.

Effect of the Invention

According to the present invention, it is possible to suppress anyharmful influence which would be otherwise exerted by the interferingsubstance contained in the sample on the detection of the objectivesubstance performed by the detecting unit in the sensor for measuringthe objective substance contained in the sample.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic arrangement of a component continuous measuringapparatus provided with an electrochemical sensor according to a firstembodiment.

FIG. 2 shows a perspective view illustrating the entire electrochemicalsensor according to the first embodiment.

FIG. 3 shows a sectional view taken along a line A-A′ indicated byarrows shown in FIG. 2.

FIG. 4 shows a perspective view illustrating an entire electrochemicalsensor according to a first modified embodiment of the first embodiment.

FIG. 5 shows a sectional view taken along a line B-B′ indicated byarrows shown in FIG. 4.

FIG. 6 shows a perspective view illustrating an entire electrochemicalsensor according to a second embodiment.

FIG. 7 shows a sectional view taken along a line C-C′ indicated byarrows shown in FIG. 6.

FIG. 8 shows an exemplary detailed arrangement of an agent accommodatingcase and a piezoelectric element of an interfering substance removingunit according to the second embodiment.

FIG. 9 shows a perspective view illustrating an entire electrochemicalsensor according to a third embodiment.

MODE FOR CARRYING OUT THE INVENTION

The sensor according to the present invention will be explained belowwith reference to the drawings. The sensor according to the mode forcarrying out the present invention will be explained as exemplified byan electrochemical sensor for measuring an objective substance byutilizing the electrochemical reaction by way of example. The structuresor arrangements of the following embodiments are described by way ofexample. The electrochemical sensor according to the mode for carryingout the present invention is not limited to the structures orarrangements of the embodiments. For example, the sizes or dimensions,the materials, the shapes, and the relative arrangement of theconstitutive elements in the respective embodiments are not intended tolimit the technical scope of the invention only thereto, unlessotherwise specifically noted. In the following drawings, the componentsor parts, which are the same as or equivalent to the components or partsdepicted in the preceding drawings, are designated by the same referencenumerals. The explanation of the respective embodiments of the sensoraccording to the present invention described below also serves as theexplanation of the respective embodiments of the method for removing theinterfering substance applied to the sensor according to the presentinvention.

First Embodiment

A first embodiment of the electrochemical sensor according to the modefor carrying out the present invention will be explained. FIG. 1 shows aschematic arrangement of a component continuous measuring apparatus 1provided with an electrochemical sensor according to the firstembodiment. The component continuous measuring apparatus 1 shown in FIG.1 can continuously measure the concentration of a specified objectivesubstance (specified objective component) contained in a sample. Thesample includes, for example, blood and intercellular fluid. Thespecified objective substance includes, for example, glucose, lacticacid, and bile acid. The component continuous measuring apparatus 1 canbe used while being attached to a human body. The component continuousmeasuring apparatus 1 is provided with a casing 2, a circuit board 3,and an electrochemical sensor 4. In the following embodiment, anexplanation will be exemplarily made about such a case that glucose,which is contained in the intercellular fluid, is used as the objectiveas the specified objective substance.

The casing 2 includes a cover 10 and a main body substrate 11. Thecircuit board 3 is accommodated in the space defined by the cover 10 andthe main body substrate 11. It is preferable that the casing 2 has thewaterproof property or the water resistant property. Materials, whichhave extremely low water permeability as exemplified, for example, bymetal and polypropylene resin, may be used for the cover 10 and the mainbody substrate 11.

The main body substrate 11 is a portion through which theelectrochemical sensor 4 is inserted. The main body substrate 11 fixes apart of the electrochemical sensor 4. An adhesive film 5 is fixed to themain body substrate 11. The adhesive film 5 is utilized when thecomponent continuous measuring apparatus 1 is fixed to the skin 6. Forexample, a tape, which has stickiness on both surfaces, can be used asthe adhesive film 5.

The circuit board 3 carries electronic parts necessary for predeterminedoperations of the component continuous measuring apparatus 1 (forexample, application of the voltage, calculation of the concentration ofthe specified objective substance, and communication with any externalapparatus). The circuit board 3 is provided with terminals 12 for makingelectric connection with respect to the electrochemical sensor 4. Theterminals 12 are utilized to apply the voltage to the electrochemicalsensor 4 and obtain the response current value from the electrochemicalsensor 4.

The electrochemical sensor 4 is the sensor to obtain the responsecorresponding to the concentration of the specified component containedin the specimen, i.e., glucose contained in the intercellular fluid inthis case. A part of the electrochemical sensor 4 protrudes from theskin 6, which is brought in contact with the terminals 12 of the circuitboard 3. Further, another part of the electrochemical sensor 4 isinserted while being implanted into the skin 6. That is, theelectrochemical sensor 4 is used while a part thereof is retained in theskin 6 (subcutaneously beneath the skin).

FIG. 2 shows a perspective view illustrating the entire electrochemicalsensor 4 according to the first embodiment. The electrochemical sensor 4has a sensor substrate 21, a detecting unit 22, lead wires 23, terminals24, and a filter 25.

The sensor substrate 21 has the insulating property and the flexibility,and the sensor substrate 21 supports the detecting unit 22. A part ofthe sensor substrate 21, which includes an end portion 21A, isaccommodated in the casing 2. Another part of the sensor substrate 21,which includes an end portion 21B disposed on the side opposite to theend portion 21A, is inserted into the skin 6. The end portion 21B of thesensor substrate 21 may have a sharp shape. When the end portion 21B ofthe sensor substrate 21 has the sharp shape, then the electrochemicalsensor 4 can be easily inserted into the skin 6, and it is possible toreduce the pain of an objective person into which the electrochemicalsensor 4 is inserted.

A material, which has the biocompatibility and the insulating property,can be used for the sensor substrate 21. It is possible to use, forexample, a resin such as polypropylene, polyimide, polyethyleneterephthalate, polyether ether ketone, polyethylene naphthalate or thelike for the sensor substrate 21. In the following description, thelongitudinal direction of the sensor substrate 21 is the direction whichis directed from the end portion 21B of the sensor substrate 21 to theend portion 21A of the sensor substrate 21 (direction in which thesensor substrate 21 is accommodated in the casing 2) or the directionwhich is directed from the end portion 21A of the sensor substrate 21 tothe end portion 21B of the sensor substrate 21 (direction in which thesensor substrate 21 is inserted into the skin 6). The widthwisedirection of the sensor substrate 21 is the direction which isperpendicular to the longitudinal direction of the sensor substrate 21.As for the sensor substrate 21, the end portion 21A is also referred toas “forward end portion 21A”, and the end portion 21B is also referredto as “proximal end portion 21B”.

A recess 21C is formed on the forward end side of the sensor substrate21, and the detecting unit 22 is provided on the surface of the recess21C. The detecting unit 22 can be formed, for example, by means of thevapor deposition, the sputtering, the printing (for example, the screenprinting, the gravure printing or the like), or the transfer printing.The detecting unit 22 includes a working electrode 22A and a counterelectrode 22B. The working electrode 22A is the portion to give andreceive electrons with respect to the specified objective substancecontained in a sample or specimen. The counter electrode 22B is utilizedto apply the voltage together with the working electrode 22A.

One end portion of each of the lead wires 23 is connected to each of theworking electrode 22A and the counter electrode 22B. Each of theterminals 24 is connected to the other end of each of the lead wires 23.The terminals 24 are brought in contact with the terminals 12 of thecircuit board 3.

The reagent enzyme is formed on (for example, applied to) the surface ofthe working electrode 22A. In this embodiment, the concentration ofglucose contained in a specimen is measured by using the electrochemicalsensor 4. Therefore, glucose oxidase (GOD), which uses glucose as thesubstrate, is adopted as the reagent enzyme. Glucose dehydrogenase (GDH)may be adopted as the reagent enzyme in place of glucose oxidase. Forexample, when the concentration of lactic acid contained in a specimenis measured, it is possible to use lactate oxidase as the reagentenzyme. As for the method for immobilizing the reagent enzyme, it ispossible to adopt various known methods including, for example, methodsto utilize polymerizable gel; high molecular weight compound such aspolyacrylamide, phosphorus or the like; MPC polymer including silanecoupling agent introduced into phospholipid polymer; and protein film.

As shown in the drawing, the filter 25 is provided on the sensorsubstrate 21 so that the working electrode 22A and the counter electrode22B are covered therewith. In particular, the filter 25 is provided sothat the entire recess 21C formed on the sensor substrate 21 is coveredtherewith and the upper end opening is closed thereby. When theelectrochemical sensor 4 is inserted into the skin 6, the detecting unit22 is not directly brought in contact with the skin 6, because thefilter 25 is provided so that the detecting unit 22 is coveredtherewith. In this way, the filter 25 also functions as the protectivefilm for protecting the detecting unit 22.

When the intercellular fluid, which is permeated into the filter 25,arrives at the surface of the working electrode 22A, glucose oxidase,which is immobilized on the surface of the working electrode 22A, causesthe reaction of glucose. The voltage is applied to glucose oxidase bymeans of the working electrode 22A and the counter electrode 22B, andthus the electrons are given and received between the working electrode22A and glucose contained in the intercellular fluid.

That is, glucose contained in the intercellular fluid is reduced(electrons are taken out) by the aid of glucose oxidase immobilized onthe working electrode 22A in the detecting unit 22, and the electronsare supplied to the working electrode 22A. The amount of electronssupplied to the working electrode 22A is measured as the responsecurrent value. As a result, an electric signal, which indicates theresponse current value as obtained when the voltage is applied, isgenerated by the electrochemical sensor 4, and the electric signal isinputted into the circuit board 3 of the component continuous measuringapparatus 1. The electric signal, which indicates the response currentvalue, is the electric signal which correlates with the glucoseconcentration. The circuit board 3 calculates the glucose concentration(blood glucose level or blood sugar level) on the basis of the responsecurrent value. The result of calculation of the glucose concentration istransmitted to an external information terminal, if necessary.

Next, an explanation will be made in detail about the filter 25 and thestructure or arrangement relevant to the filter 25. The filter 25 is themember having such function that the permeation into the interior of therecess 21C is permitted for glucose as the specified objective substanceon one hand, the permeation is regulated (permeation is prohibited) forthe interfering substance that interferes in the reaction of glucosecaused by glucose oxidase as the reagent enzyme, i.e., the enzymaticreaction of glucose oxidase on the other hand, and the interferingsubstance is collected.

The interfering substance includes, for example, microorganisms (forexample, bacteria and fungi), protein, fibrin, and lipid contained inthe specimen. If the microorganism exists around the detecting unit 22,then glucose oxidase is destroyed by the microorganism, and/or glucoseand oxygen are consumed. The enzymatic reaction of glucose oxidase isaffected thereby. If the protein and/or fibrin adhere/adheres to thedetecting unit 22, glucose hardly arrives at the detecting unit 22, forexample, due to the formation of the foreign body capsule (FBC) asdescribed above. The enzymatic reaction of glucose oxidase is alsoaffected thereby. If such a situation arises, for example, it is fearedthat the measurement accuracy of the glucose concentration may beconsequently deteriorated. In view of the above, the interferingsubstance, which includes, for example, the protein and themicroorganism contained in the specimen, is filtrated by the filter 25so that the interfering substance is prevented from arriving at thedetecting unit 22 to which glucose oxidase is immobilized.

The electrochemical sensor 4 of this embodiment is of the so-calledsubcutaneous retention type. The measurement duration period is set sothat the glucose concentration is continuously measured for a relativelylong period of time. For example, the measurement duration period lastsfor several weeks in some cases. When the subcutaneous retention periodof the electrochemical sensor 4 lasts for a long period of time asdescribed above, then the amount of collection of the interferingsubstance collected by the filter 25, i.e., the amount of adhesion(amount of accumulation) of the interfering substance on the filter 25is excessively increased, and it is feared that the filter 25 may be,for example, consequently clogged up. As a result, it is feared that thesmooth arrival of glucose may be inhibited with respect to glucoseoxidase retained on the working electrode 22A of the detecting unit 22.In view of the above, the electrochemical sensor 4 removes theinterfering substance adhered to the filter 25 by means of aninterfering substance removing unit 8 explained below. The interferingsubstance is removed by the interfering substance removing unit 8 in astate in which the filter 25 is exposed to the specimen (intercellularfluid), i.e., during the subcutaneous retention period in which theelectrochemical sensor 4 is subcutaneously retained beneath the skin.The method for removing the interfering substance adhered to theelectrochemical sensor 4 according to the present invention has thefollowing feature. That is, the method comprises allowing theinterfering substance to adhere to the filter 25 beforehand by coveringthe detecting unit 22 with the filter 25, and removing the interferingsubstance adhered to the filter 25 by means of the interfering substanceremoving unit 8 which removes the interfering substance.

A material, which has the biocompatibility, can be used for the filter25. As for the filter 25, it is possible to use, for example,polyurethane, silicone-based polymer (polysiloxane), cellulose acetate,hydrogel, polyvinyl alcohol, HEMA (hydroxyethyl methacrylate), andcopolymer containing any one of them. The filter 25 can be formed, forexample, by means of the spin coat, the dip coat, or the drop coat.

An explanation will be made below with reference to FIGS. 2 and 3 aboutthe detailed structure or arrangement of the interfering substanceremoving unit 8 according to the first embodiment. FIG. 3 shows asectional view taken along a line A-A′ indicated by arrows shown in FIG.2. This sectional view shows a cross-sectional structure as obtainedwhen the recess 21C of the sensor substrate 21 is cut or sectioned inthe widthwise direction.

The interfering substance removing unit 8 removes the interferingsubstance accumulated or deposited on the filter 25, by vibrating thefilter 25. The interfering substance removing unit 8 is constructed toinclude a piezoelectric element (piezo-element) 81 and vibrationtransmitting members 82. The piezoelectric element 81 is provided on thesensor substrate 21. In the example shown in FIG. 2, the shape of theupper end opening, which is provided for the recess 21C, is rectangular.The piezoelectric element 81 is arranged at a position disposed closelyto the filter 25 along one upper end opening edge of the recess 21C. Thepiezoelectric element 81 is constructed by a piezoelectric member 810which is deformable by applying a voltage, and two electrodes 811 whichare connected to interpose the piezoelectric member 810 therebetween.The piezoelectric element 810 is a well-known element, and hence anydetailed explanation thereof is omitted. In this specification, thedirection, which is perpendicular to both of the longitudinal directionand the widthwise direction of the sensor substrate 21 (i.e., thedirection perpendicular to the in-plane direction of the sensorsubstrate 21), is defined as “upward-downward direction”.

An AC power source 7, which is provided to apply the AC voltage to thepiezoelectric element 81, is accommodated in the casing 2 of thecomponent continuous measuring apparatus 1. The electrodes 811, 811 ofthe piezoelectric element 81 are connected to the AC power source 7 vialead wires 7A and terminals 7B. The lead wires 7A and the AC powersource 7 shown in FIG. 3 are schematically depicted in relation to theelectric connection with respect to the piezoelectric element 81. The ACpower source 7 is capable of performing the output, for example, withina range of ±0.2 V to ±24 V for the voltage and a range of 0.001 Hz to1000 MHz for the frequency. However, these numerical ranges are providedby way of example.

When the AC voltage is applied from the AC power source 7 to thepiezoelectric element 81, the piezoelectric element 81 is vibrated byperiodically repeating the expanding/contracting deformation. As shownin FIG. 3, the electrodes 811 are stuck to the upper and lower surfacesof the piezoelectric member 810. Therefore, the piezoelectric element 81repeats the expanding/contracting deformation in the upward-downwarddirection. The control, which relates to the voltage application by theAC power source 7, is performed by the circuit board 3 of the componentcontinuous measuring apparatus 1.

In this context, the phenomenon, in which the electric polarization isinduced by applying the force to a crystal in a certain specifieddirection to generate the positive and negative electric charges, isreferred to as “piezoelectric effect”. The phenomenon, in which thestrain is generated in proportion to the voltage when the voltage isapplied to a certain crystal, is referred to as “inverse piezoelectriceffect”. In the embodiment according to the present invention, theinverse piezoelectric effect is utilized. When the electric field isapplied in parallel to the polarization direction, then the rotationalforce is generated in electric dipoles which are aligned on a straightline, the change in length is generated in the single crystal thereby,and the strong torque is consequently generated. For example, leadzirconate titanate (Pb(Zr,Ti)O3) is preferably employed as the materialto be used for the piezoelectric member 810, which is generallyabbreviated and referred to as PZT (piezo). The filter 25 is vibrated bythe aid of the vibration transmitting members 82 as described later onby utilizing the torque and the length change of the piezoelectricmember 810 generated by applying the voltage between the electrodes 811.Accordingly, it is possible to remove the interfering substance adheredto the filter 25.

The vibration transmitting member 82 is the member which is connected tothe piezoelectric element 81 and which transmits the vibrational energyof the piezoelectric element 81 to the filter 25. As shown in thedrawing, the vibration transmitting member 82 is the slenderplate-shaped member constructed to have one end which is fixed to thepiezoelectric element 81 and the other end which behaves as a free end.The vibration transmitting members 82 are arranged along the uppersurface of the filter 25. When the vibration transmitting member 82 isvibrated in the upward-downward direction shown in FIG. 2 in cooperationwith the expanding/contracting deformation of the piezoelectric element81, the vibration transmitting member 82 collides with the filter 25when the vibration transmitting member 82 is displaced in the directionto make approach to the filter 25 (alternate long and two short dashesline shown in FIG. 3 schematically illustrates the situation ofvibration of the vibration transmitting member 82). Accordingly, thevibrational energy of the piezoelectric element 81 is transmitted to thefilter 25, and the interfering substance, which is accumulated on thefilter 25, is exfoliated from the filter 25 by the impact exertedthereby.

The vibration transmitting member 82 may be arranged in such a mode thatthe vibration transmitting member 82 is always brought in contact withthe filter 25. The vibration transmitting member 82 may be fixed to thelower surface other than the upper surface of the piezoelectric element81. In a more specified mode, for example, the vibration transmittingmember 82 may be interposed between the lower surface of thepiezoelectric element 81 and the sensor substrate 21. In any case, whenthe vibration transmitting member 82 is vibrated, then the vibrationalenergy is transmitted to the filter 25, and the interfering substance,which is adhered to the filter 25, is appropriately removed. In thisembodiment, the vibrational energy of the piezoelectric element 81 istransmitted to the filter 25 by the aid of the vibration transmittingmember 82. However, the piezoelectric element 81 may directly vibratethe filter 25.

As described above, when the interfering substance removing unit 8 isoperated by the voltage applied from the AC power source 7, it ispossible to remove the interfering substance adhered to the filter 25which is in the state of being exposed to the specimen. Therefore, evenwhen the subcutaneous retention period of the electrochemical sensor 4lasts for a long period of time, the amount of adhesion (amount ofaccumulation) of the interfering substance to the filter 25 issuppressed from being excessively increased, for example, byperiodically performing the process for removing the interferingsubstance. Thus, it is possible to secure the smooth reaction of glucoseas the specified objective substance caused by the reagent enzyme. Inother words, when the glucose concentration is measured, it is possibleto suppress the influence which would be otherwise exerted by theinterfering substance contained in the sample on the reaction of glucosecaused by the reagent enzyme.

The control (hereinafter referred to as “interfering substance removingcontrol”), under which the interfering substance accumulated on thefilter 25 is removed, may be carried out at every constant periodsduring the measurement duration period for measuring the glucoseconcentration. As a result, it is possible to suppress the excessiveincrease in the amount of adhesion of the interfering substance to thefilter 25. It is also preferable to carry out the interfering substanceremoving control when any sign or indication, which indicates thatglucose hardly arrives at the detecting unit 22, is found from thechange or transition of the calculation result of the glucoseconcentration. The execution timing of the interfering substanceremoving control referred to in this section is applicable to otherembodiments and modified embodiments described later on.

As shown in FIG. 2, the interfering substance removing unit 8 accordingto this embodiment is provided with the plurality of vibrationtransmitting members 82. Accordingly, the vibrational energy can beefficiently transmitted to the entire filter 25, and the interferingsubstance can be removed more appropriately. However, the mode forcarrying out the present invention is not limited thereto. Thevibrational energy of the piezoelectric element 81 may be transmitted tothe filter 25 by using the single vibration transmitting member 82. Inthis embodiment, the shape or form of the vibration transmitting member82 is the slender plate-shaped form. However, it is also allowable toadopt any other shape or form. For example, it is also preferable toadopt a slender rod-shaped form. This embodiment is illustrative of suchan exemplary case that only one piezoelectric element 81 is arranged onthe sensor substrate 21. However, for example, it is also allowable toarrange a plurality of piezoelectric elements 81 so that thepiezoelectric elements 81 correspond to the respective vibrationtransmitting members 82.

In the first embodiment, the recess 21C is formed on the forward endside of the sensor substrate 21, and the detecting unit 22 is arrangedin the recess 21C. However, the mode for carrying out the presentinvention is not limited thereto. That is, even when the recess 21C isnot formed, the present invention can be appropriately applied. In thiscase, for example, a detecting unit 22 may be formed on the forward endside of a flat sensor substrate 21, and a filter 25 may be provided tocover the detecting unit 22 therewith. The effect, which is the same asor equivalent to that of the first embodiment, can be also provided inaccordance with the mode as described above. The concerning matter alsoholds equivalently in relation to other embodiments and modifiedembodiments described later on.

The first embodiment is illustrative of such an exemplary case that oneworking electrode 22A and one counter electrode 22B are arranged on thesensor substrate 21 respectively. However, the mode for carrying out thepresent invention is not limited thereto. It is also allowable that aplurality of detecting units 22 are provided on the sensor substrate 21.Further, a plurality of working electrodes 22A may be provided on thesensor substrate 21, and a plurality of counter electrodes 22B may beprovided on the sensor substrate 21. When the plurality of workingelectrodes 22A are provided on the sensor substrate 21, the measurementof the glucose concentration in the intercellular fluid can be continuedeven when any malfunction such as any failure or the like arises in oneworking electrode 22A. Further, when the plurality of counter electrodes22B are provided on the sensor substrate 21, the measurement of theglucose concentration in the intercellular fluid can be continued evenwhen any malfunction such as any failure or the like arises in onecounter electrode 22B. When the plurality of counter electrodes 22B areprovided on the sensor substrate 21, it is possible to measure analysisobjective items which are different from each other. That is, when theplurality of counter electrodes 22B are provided on the sensor substrate21, it is possible to measure a plurality of types of specifiedcomponents contained in a specimen.

First Modified Embodiment

A first modified embodiment of the first embodiment will be explained.FIG. 4 shows a perspective view illustrating an entire electrochemicalsensor 4A according to the first modified embodiment of the firstembodiment. Reference numeral 8A indicates an interfering substanceremoving unit according to the first modified embodiment. Anelectrochemical sensor 4A according to this modified embodiment isconstructed in the same manner as in the first embodiment except for theinterfering substance removing unit 8A. The interfering substanceremoving unit 8A also removes the interfering substance accumulated onthe filter 25, by vibrating the filter 25. The interfering substanceremoving unit 8A is constructed to include a piezoelectric element 81, avibration transmitting member 82A, and a fixed member 83. The members ofthe electrochemical sensor 4A shown in FIG. 4, which are common to thoseof the electrochemical sensor 4 of the first embodiment, are designatedby the common reference numerals, any detailed explanation of which willbe omitted thereby.

FIG. 5 shows a sectional view taken along a line B-B′ indicated byarrows shown in FIG. 4. As shown in FIG. 5, the piezoelectric element 81has two electrodes 811 which are stuck to side surfaces of apiezoelectric member 810. The electrodes 811, 811 are connected to theAC power source 7 via the lead wires 7A and the terminals 7Brespectively. The AC voltage is applied from the AC power source 7 tothe piezoelectric element 81 constructed as described above.Accordingly, the piezoelectric element 81 repeats theexpanding/contracting deformation in the in-plane direction of thesensor substrate 21. In the exemplary arrangement shown in FIG. 5, thepiezoelectric element 81 repeats the expanding/contracting deformationin the widthwise direction of the sensor substrate 21.

The vibration transmitting member 82A has a shape different from that ofthe vibration transmitting member 82 described in the first embodiment.The vibration transmitting member 82A is a planar or sheet-shaped memberhaving a grid (lattice) structure or a mesh structure. The vibrationtransmitting member 82A has the rigidity to some extent. The fixedmember 83 is arranged along the upper end opening edge of the recess 21Cso that the fixed member 83 is opposed to the piezoelectric element 81with the recess 21C intervening therebetween. The fixed member 83 is theimmovable member fixed to the sensor substrate 21.

The vibration transmitting member 82A is fixed to the upper surface ofthe piezoelectric element 81 and the upper surface of the fixed member83. When the piezoelectric element 81 is vibrated in the widthwisedirection of the sensor substrate 21 in accordance with the applicationvoltage from the AC power source 7, the horizontal spacing distancebetween the piezoelectric element 81 and the fixed member 83 is changed.The rigidity of the vibration transmitting member 82A is relativelyhigh. Therefore, the vibration transmitting member 82A is warped (bent)in the upward-downward direction, and the vibration transmitting member82A is consequently vibrated in accordance with the change of thehorizontal spacing distance as described above (alternate long and twoshort dashes lines shown in FIG. 5 schematically show the situation inwhich the vibration transmitting member 82A is vibrated in theupward-downward direction). Accordingly, the vibration transmittingmember 82A periodically collides with the filter 25, and the vibrationalenergy thereof is transmitted to the filter 25. As a result, it ispossible to exfoliate the interfering substance adhered to the filter25, and it is possible to appropriately remove the interferingsubstance.

In this modified embodiment, the vibration transmitting member 82A isfixed to the upper surfaces of the piezoelectric element 81 and thefixed member 83. However, there is no limitation thereto. For example,the vibration transmitting member 82A may be interposed between the sidesurface of the piezoelectric element 81 and the side surface of thefixed member 83. Alternatively, the vibration transmitting member 82Amay be fixed to the lower surface of the piezoelectric element 81 andthe lower surface of the fixed member 83 in such a mode that thevibration transmitting member 82A is interposed with respect to thesensor substrate 21. According to the mode as described above, thehorizontal spacing distance between the piezoelectric element 81 and thefixed member 83 is also changed in accordance with the vibration of thepiezoelectric element 81, and it is possible to vibrate the vibrationtransmitting member 82A in the upward-downward direction. It is alsoallowable that the filter 25 and the vibration transmitting member 82Ahas an integrated structure. For example, the filter 25 may be formed asa film in the grid or lattice of the vibration transmitting member 82A.Alternatively, the piezoelectric element 81 and the single unit of thefilter 25 may be arranged while being brought in contact with each otherwithout using the vibration transmitting member 82A. Accordingly, thevibrational energy of the piezoelectric element 81 may be directlytransmitted to the filter 25 thereby, and thus the filter 25 may bevibrated. In the mode for carrying out the present invention, aplurality of piezoelectric elements 81 may be arranged on the sensorsubstrate 21.

Each of the vibration transmitting member 82 referred to in the firstembodiment described above and the vibration transmitting member 82Areferred to in the first modified embodiment may be formed as a meshwhich is biocompatible, which is prepared by weaving monofilament ormultifilament fibers composed of any material including syntheticmaterials and various organic matters, and which has pores or holes ofvarious dimensions and geometrical forms, in the same manner as abiocompatible mesh structure described, for example, in Japanese PatentApplication Laid-Open No. 2004-524059 (P2004-524059A). Specifically, forexample, each of the vibration transmitting member 82 and the vibrationtransmitting member 82A may be formed of polypropylene,polytetrafluoroethylene, polytetrafluoroethylene foam, polyethyleneterephthalate, polyglycolic acid, polyglactin, dacron-polythenereinforced silicone, or polyethylene. For example, as described inJapanese Patent Application Laid-Open No. 2010-508897 (P2010-508897A),each of the vibration transmitting member 82 and the vibrationtransmitting member 82A may be produced by adopting a material which isthe same as or equivalent to that of a biocompatible mesh structurecomposed of a plurality of mutually connected strands provided with aplurality of gaps or interstices formed therebetween.

Second Embodiment

A second embodiment of the electrochemical sensor according to the modefor carrying out the present invention will be explained. FIG. 6 shows aperspective view illustrating an entire electrochemical sensor 4Baccording to the second embodiment. The members of the electrochemicalsensor 4B, which are common to those of the electrochemical sensors 4,4A, are designated by the common reference numerals, any detailedexplanation of which will be omitted thereby. The electrochemical sensor4B is also provided with an interfering substance removing unit 8B forremoving the interfering substance contained in a specimen adhered tothe filter 25. The interfering substance removing unit 8B removes theinterfering substance adhered to the filter 25 by supplying an agent fordecomposing the interfering substance to the filter 25. An explanationwill be made below about a specified structure or arrangement of theinterfering substance removing unit 8B according to this embodiment.

FIG. 7 shows a sectional view taken along a line C-C′ indicated byarrows shown in FIG. 6. The interfering substance removing unit 8B isconstructed by a piezoelectric element 81 and an agent accommodatingcase 84. The agent accommodating case 84 is the case which accommodatestherein an agent for removing the interfering substance. The agent mayinclude, for example, anticoagulant, protease (protein degradingenzyme), and lipase (lipid degrading enzyme). However, any agent otherthan the above may be accommodated in the agent accommodating case 84.

As shown in FIG. 6, the agent accommodating case 84 is arranged at aposition disposed closely to the filter 25 along one upper end openingedge of the recess 21C. Discharge holes 84A are formed to be open on theagent accommodating case 84 in order that the agent stored therein isdischarged toward the filter 25 as described later on. The plurality(three in this embodiment) of discharge holes 84A are formed for theagent accommodating case 84 in the longitudinal direction of the sensorsubstrate 21. The respective discharge holes 84A confront the filter 25which covers the recess 21C.

The surface of the agent accommodating case 84, on which the dischargeholes 84A are formed, is referred to as “front surface”, and thesurface, which is disposed on the side opposite thereto, is referred toas “back surface”. The piezoelectric element 81 is provided on thesensor substrate 21 so that the piezoelectric element 81 is brought incontact with the back surface of the agent accommodating case 84. Thepiezoelectric element 81 is constructed by a piezoelectric member 810,and two electrodes 811, 811 which interpose the piezoelectric member 810on side surfaces thereof, in the same manner as in the first embodiment.The respective electrodes 811, 811 are connected to the AC power source7 via lead wires 7A and terminals 7B. The AC voltage is applied from theAC power source 7 to the piezoelectric element 81 in the same manner asin the other embodiments.

When the AC voltage is applied to the piezoelectric element 81 by the ACpower source 7, the piezoelectric element 81 is vibrated in thehorizontal direction in relation to the sensor substrate 21. In thisarrangement, the back surface of the agent accommodating case 84 abutsagainst the side surface of the piezoelectric element 81. Therefore, thevibrational energy of the piezoelectric element 81 is transmitted to theagent accommodating case 84, and the back surface is pressed. As aresult, the agent accommodating case 84 is vibrated, and the agent,which is stored therein, is discharged from the discharge holes 84Atoward the filter 25. As a result, the agent contained in the agentaccommodating case 84 is sprinkled onto the filter 25. Accordingly, theinterfering substance, which adheres to the filter 25, is decomposed andremoved. For example, the protein, which is accumulated on the filter,is degraded by protease, and the lipid is degraded by lipase.

According to the electrochemical sensor 4B of this embodiment, the freshagent, which is prepared to remove the interfering substance, can besupplied to the filter 25 at any time during the measurement durationperiod (for example, during the subcutaneous retention period).Accordingly, the interfering substance can be removed more efficientlyas compared with a case in which the filter 25 is previously impregnatedwith the agent.

This embodiment is illustrative of such an exemplary case that the threedischarge holes 84A are formed through the agent accommodating case 84.However, it is a matter of course that the number thereof may bechanged. The number may be determined on the basis of the parameterincluding, for example, the surface area of the filter 25, thecross-sectional area of the discharge hole 84A, and the voltage appliedto the piezoelectric element 81. Alternatively, the interior of theagent accommodating case 84 may be comparted into a plurality ofaccommodating chambers. In this case, agents of different types may beaccommodated in the respective accommodating chambers. Furtheralternatively, a plurality of agent accommodating cases 84 may bearranged on the sensor substrate 21 so that the filter 25 is surroundedthereby.

An explanation will now be made about an exemplary detailed arrangementof the agent accommodating case 84 and the piezoelectric element 81.FIG. 8 shows the exemplary detailed arrangement of the agentaccommodating case 84 and the piezoelectric element 81 of theinterfering substance removing unit 8B. The agent accommodating case 84and the piezoelectric element 81 according to this embodiment can beconstructed in the same manner as a liquid discharge head described, forexample, in Japanese Patent Application Laid-Open No. 2011-25632A(P2011-25632A).

In the exemplary case shown in the drawing, the piezoelectric element 81is provided on the back surface side of the agent accommodating case 84.An agent accommodating portion 840, which is a hollow space capable ofaccommodating the agent, is formed at the inside of the agentaccommodating case 84. The discharge hole 84A, from which the agent isdischarged to the outside, is formed on a front surface wall of theagent accommodating case 84. The agent accommodating portion 840 and thedischarge hole 84A are communicated with each other via a first agentsupply flow passage 841, a throttle 842, a liquid pressurizing chamber843, and a second agent supply flow passage 844. The back surface of theagent accommodating case 84 forms an opening. The opening is closed bythe piezoelectric element 81 which is adhered to the agent accommodatingcase 84.

As shown in the drawing, the agent accommodating case 84 has a stackedstructure which is constructed by stacking a plurality of plates. Theplates are a cavity plate 845, a supply plate 846, an accommodatingplate 847, a cover plate 848, and a nozzle plate 849 as referred to inthis order starting from the side of the piezoelectric element 81. Alarge number of holes are formed for the plates. The respective plates845 to 849 are stacked by the aid of adhesive layers so that therespective holes are communicated with each other. Thus, for example,the agent accommodating portion 840, the first agent supply flow passage841, the throttle 842, the liquid pressurizing chamber 843, the secondagent supply flow passage 844, and the discharge hole 84A are formed. Inthe exemplary structure shown in FIG. 8, the liquid pressurizing chamber843 approximately has a depth thereof of 10 to 200 μm, a width of 100 to1000 μm, and a length of 200 to 2000 μm. The throttle 842 approximatelyhas a depth thereof of 0.05 to 1 μm, a width of 100 to 1000 μm, and alength of 10 to 100 μm. However, there is no limitation to the sizes ordimensions described above.

As for the plates 845 to 849 as described above, the plates may bemanufactured, for example, by means of the rolling method. After that,the holes, which are to be formed into the agent accommodating portion840, the first agent supply flow passage 841, the liquid pressurizingchamber 843, the second agent supply flow passage 844, and the dischargehole 84A, may be processed to have predetermined shapes by means of theetching, and the portion, which is to be formed into the throttle 842,may be manufactured by means of the half etching. Each of the plates 845to 849 may be formed of at least one metal selected from the groupconsisting of those based on Fe—Cr, Fe—Ni, and WC—TiC.

In the next place, the piezoelectric element 81 has the stackedstructure composed of piezoelectric ceramic layers 810 a, 810 b whichare two piezoelectric members. Each of the piezoelectric ceramic layer810 a, 810 b has a thickness of about 20 μm. Therefore, the entirepiezoelectric element 81 has a thickness of about 40 μm. Each of thepiezoelectric ceramic layer 810 a, 810 b is composed of, for example, aceramics material based on lead zirconate titanate (PZT) having theferroelectric property.

The piezoelectric element 81 has a first electrode 811 a which iscomposed of a metal material such as those based on Ag—Pd or the likeand a second electrode 811 b which is composed of a metal material suchas those based on Au or the like. In this exemplary arrangement, thepiezoelectric ceramic layer 810 a, the first electrode 811 a, thepiezoelectric ceramic layer 810 b, and the second electrode 811 b areprovided in this order as referred to from those disposed nearer to theback surface of the agent accommodating case 84. In other words, thefirst electrode 811 a and the second electrode 811 b are arranged sothat only the piezoelectric ceramic layer 810 b, which is positioned onthe outer side, is interposed. The area of the piezoelectric ceramiclayer 810 b, which is interposed by the second electrode 811 b and thefirst electrode 811 a, is referred to as “active portion”. Thepiezoelectric ceramic material, which is disposed at the concerningportion, is polarized. In the case of the piezoelectric element 81 ofthis exemplary arrangement, only the piezoelectric ceramic layer 810 b,which is disposed on the outer side, includes the active portion. Thepiezoelectric ceramic layer 810 a does not include any active portion,which functions as a vibration plate. Therefore, the piezoelectricelement 81 has the so-called unimorph type structure.

The piezoelectric element 81 and the agent accommodating case 84, whichare constructed as described above, are adhered to one another, forexample, by the aid of an adhesive layer. As for the adhesive layer, itis also allowable to use an adhesive of, for example, a thermosettingresin such as epoxy resin, phenol resin, polyphenylene ether resin orthe like.

As shown in FIG. 7 as well, the first electrode 811 a and the secondelectrode 811 b are connected to the AC power source 7 via the leadwires 7A and the terminals 7B. The AC voltage from the AC power source 7is applied to the piezoelectric element 81. When the voltage is appliedto the piezoelectric ceramic layer 810 b in the polarization directionthereof while allowing the second electrode 811 b to have an electricpotential different from that of the first electrode 811 a, the portion,to which the voltage is applied, functions as the active portion whichis strained in accordance with the piezoelectric effect. In thissituation, the piezoelectric ceramic layer 810 b is expanded orcontracted in the thickness direction, i.e., in the stacking direction,and the piezoelectric ceramic layer 810 b is contracted or expanded inthe direction perpendicular to the stacking direction, i.e., in thein-plane direction in accordance with the piezoelectric transversal(lateral) effect. On the other hand, the remaining piezoelectric ceramiclayer 810 a is the inactive layer which does not have any areainterposed by the second electrode 811 b and the first electrode 811 a.Therefore, the remaining piezoelectric ceramic layer 810 a is notdeformed spontaneously. That is, the piezoelectric ceramic layer 810 a,which is the inactive layer, is not affected by the electric field.Therefore, the piezoelectric ceramic layer 810 a is not shrunkspontaneously, and the piezoelectric ceramic layer 810 a intends toregulate the deformation of the active portion. As a result, thedifference arises in the strain in the polarization direction betweenthe piezoelectric ceramic layer 810 b and the piezoelectric ceramiclayer 810 a. The piezoelectric ceramic layer 810 b is deformed(subjected to the unimorph deformation) so that the piezoelectricceramic layer 810 b protrudes toward the liquid pressurizing chamber843.

An explanation will be made about the specified control contentsprovided when the agent, which is accommodated in the agentaccommodating case 84, is discharged from the discharge hole 84A. As forthe control contents, the second electrode 811 b is previously allowedto have the electric potential (hereinafter referred to as “highelectric potential”) higher than that of the first electrode 811 a. Thesecond electrode 811 b is once allowed to have the same electricpotential (hereinafter referred to as “low electric potential”) as thatof the first electrode 811 a every time when the discharge request isgiven. After that, the second electrode 811 b is allowed to have thehigh electric potential again at a predetermined timing. Accordingly,the piezoelectric ceramic layers 810 a, 810 b are returned to theoriginal shapes at a timing at which the second electrode 811 b isallowed to have the low electric potential. The volume of the liquidpressurizing chamber 843 is increased as compared with the initial state(state in which the electric potentials of the both electrodes aredifferent from each other). In this situation, the negative pressure isapplied to the interior of the liquid pressurizing chamber 843, and theagent is sucked into the liquid pressurizing chamber 843 from the sideof the agent accommodating portion 840.

After that, the piezoelectric ceramic layers 810 a, 810 b are deformedso that the piezoelectric ceramic layers 810 a, 810 b protrude towardthe liquid pressurizing chamber 843 at a timing at which the secondelectrode 811 b is allowed to have the high electric potential again.The pressure in the liquid pressurizing chamber 843 is the positivepressure on account of the decrease in the volume of the liquidpressurizing chamber 843, and the agent is discharged from the dischargehole 84A. The electric power application, which is effected by the ACpower source 7, is controlled as described above. Accordingly, the agentcan be sprinkled onto the filter 25 from the discharge hole 84A at thedesired timing. It is possible to decompose and remove the interferingsubstance adhered to the filter 25.

In the exemplary arrangement shown in FIG. 8, the liquid pressurizingchamber 843 approximately has a depth thereof of 10 to 200 μm, a widthof 100 to 1000 μm, and a length of 200 to 2000 μm. The throttle 842approximately has a depth thereof of 0.05 to 1 μm, a width of 100 to1000 μm, and a length of 10 to 100 μm. However, there is no limitationto the dimensions or sizes described above.

It is a matter of course that the structure, the constitutive materials,and other features of the piezoelectric element 81, which have beendescribed with reference to FIG. 8, can be appropriately applied to anypiezoelectric element 81 of any other embodiment.

Third Embodiment

An explanation will be made about a third embodiment of theelectrochemical sensor according to the mode for carrying out thepresent invention. FIG. 9 shows a perspective view illustrating anentire electrochemical sensor 4C according to the third embodiment. Themembers of the electrochemical sensor 4C, which are common to those ofthe electrochemical sensors 4, 4A, 4B, are designated by the commonreference numerals, any detailed explanation of which will be omittedthereby. The electrochemical sensor 4C is also provided with aninterfering substance removing unit 8C which is provided to remove theinterfering substance collected on a filter.

The filter 35 according to this embodiment is the same as or equivalentto the filter 25 in that the filter 35 has the function to permit thepermeation of glucose as the specified objective substance on one handand regulate the permeation of the interfering substance on the otherhand. The filter 35 is constructed so that the internal electricalresistance thereof is higher than the electrical resistance of aspecimen (intercellular fluid in this case). In this embodiment, thefilter 35 is composed of an insulator or insulating material. The filter35 can be formed by using, for example, ceramics, glass, or syntheticresin.

The interfering substance removing unit 8C is provided with a pair ofremoving process electrodes 85A, 85B which are used in order that theinterfering substance adhered to the filter 35 is removed from thefilter 35. The removing process electrodes 85A, 85B are provided on thesensor substrate 21. The removing process electrodes 85A, 85B arearranged in such a state that the filter 35 is interposed from the bothsides thereof and the removing process electrodes 85A, 85B are broughtin contact with the filter 35. As shown in the drawing, the removingprocess electrodes 85A, 85B are provided to extend along a pair ofopposing upper end opening edges of the recess 21C. The removing processelectrodes 85A, 85B are connected to the AC power source 7 via the leadwires 7A and the terminals 7B. The removing process electrodes 85A, 85Bare, for example, platinum electrodes. However, the material for theremoving process electrodes 85A, 85B is not limited thereto.

The filter 35, which is interposed between the removing processelectrodes 85A, 85B, is an insulator. Therefore, when the AC voltage isapplied between the removing process electrodes 85A, 85B by means of theAC power source 7, the electricity flows along such a route that theelectrical resistance is lower and the route length is shorter. In thisembodiment, the filter 35 is interposed between the removing processelectrodes 85A, 85B. In this situation, the electricity may highlypossibly flow along the surface of the filter 35 when the voltage isapplied between the removing process electrodes 85A, 85B by means of theAC power source 7.

In the meantime, the intercellular fluid can be grasped as theelectrolyte. Therefore, when the voltage is applied between the removingprocess electrodes 85A, 85B immersed in the intercellular fluid, theremoving process electrodes 85A, 85B are subjected to the electrolysis.That is, the interfering substance, which adheres to the removingprocess electrodes 85A, 85B, is removed in accordance with the action ofthe electrolytic cleaning. This action will be described in more detailbelow. When the voltage is applied between the removing processelectrodes 85A, 85B, then the negative ion is attracted to the anode,and the electron is deprived from the intercellular fluid to cause theoxidation. On the other hand, the positive ion is attracted to thecathode, and thus the electron is given to the intercellular fluid tocause the reduction. The removing process electrodes 85A, 85B aresubjected to the electrolysis in accordance with the chemical action ofoxidation/reduction as described above. Oxygen gas is produced locally(microscopically) from the anode, and hydrogen gas is produced locallyfrom the cathode.

In the case of the interfering substance removing unit 8C of thisembodiment, the interfering substance, which adheres to the removingprocess electrodes 85A, 85B, is exfoliated by utilizing the physicaleffect caused by the force of the bubble of the gas generated from theremoving process electrodes 85A, 85B, for example, the agitating actioncaused by the gas. In this arrangement, the respective removing processelectrodes 85A, 85B are arranged in such a mode that they are brought incontact with the filter 35. Therefore, the interfering substance, whichadheres to the removing process electrodes 85A, 85B and the filter 35,is joined or linked together and formed as a set. For example, theinterfering substance, which adheres to the removing process electrodes85A, 85B and the filter 35, is joined or linked together to form theforeign body capsule (FBC). In other words, in the electrochemicalsensor 4C of this embodiment, the removing process electrodes 85A, 85Band the filter 35 are arranged while being brought in contact with eachother so that the interfering substance, which adheres to the removingprocess electrodes 85A, 85B and the filter 35, is formed while beingjoined or linked (connected) together.

Therefore, when the interfering substance is exfoliated from theremoving process electrodes 85A, 85B by performing the electrolyticcleaning with respect to the removing process electrodes 85A, 85B asdescribed above, the interfering substance is also exfoliated from thefilter 35 in cooperation therewith. In this way, it is possible toremove the interfering substance adhered to the filter 35, i.e., it ispossible to remove the foreign body capsule (FBC) formed on the filter35, in cooperation with the electrolytic cleaning for the removingprocess electrodes 85A, 85B.

Further, in this embodiment, the AC voltage from the AC power source 7is applied to the removing process electrodes 85A, 85B. Therefore, theboth polarities are alternated in a pulsed manner. Therefore, thecleaning efficiency is improved for the removing process electrodes 85A,85B, and the interfering substance, which adheres to the filter 35, canbe finally removed more efficiently. In the electrochemical sensor 4C ofthis embodiment, the removing process electrodes 85A, 85B and the filter35 are arranged while being brought in contact with each other. However,the mode for carrying out the present invention is not limited thereto.The removing process electrodes 85A, 85B and the filter 35 may bearranged while being disposed closely to one another, provided that thearrangement is in such a mode that the interfering substance, whichadheres to the removing process electrodes 85A, 85B and the filter 35,is formed while being joined or linked together.

The present invention has been explained above. However, the techniques,which relate to the electrochemical sensor according to the presentinvention, are not limited thereto. It is possible to includecombinations thereof as far as possible. Various changes ormodifications may be applied or added to the embodiments described abovewithin a range without deviating from the gist or essentialcharacteristics of the present invention. For example, the presentinvention is applicable to any sensor other than the electrochemicalsensor. The present invention may be applied, for example, to a sensorof such a type that a color developing reagent enzyme, whichspecifically causes the reaction of an objective substance, ispreviously retained in a detecting unit for detecting the objectivesubstance contained in a sample, and the objective substance is measuredin accordance with the colorimetric method for measuring the intensityat a color developing wavelength by means of an optical device orapparatus.

PARTS LIST

1: component continuous measuring apparatus, 2: casing, 3: circuitboard, 4, 4A, 4B, 4C: electrochemical sensor, 5: adhesive film, 6: skin,7: AC power source, 8, 8A, 8B, 8C: interfering substance removing unit,21: sensor substrate, 21C: recess, 22: detecting unit, 22A: workingelectrode, 22B: counter electrode, 25, 35: filter, 81: piezoelectricelement, 82: vibration transmitting member, 83: fixed member, 84: agentaccommodating case, 84A: discharge hole.

1.-5. (canceled)
 6. A sensor for measuring an objective substancecontained in a sample, the sensor comprising: a substrate; a detectingunit which is provided on the substrate and which detects the objectivesubstance; a filter which covers the detecting unit, which permitspermeation of the objective substance on one hand, and which regulatespermeation of an interfering substance contained in the sample on theother hand; and a removing unit which removes the interfering substanceadhered to the filter, wherein: the removing unit has at least a pair ofremoving electrodes which are arranged in mutual contact with the filteror closely to the filter; and the interfering substance adhered to thefilter is removed by means of electrolytic cleaning for the removingelectrodes performed by applying a voltage between the removingelectrodes.
 7. The sensor according to claim 6, wherein the removingelectrodes are arranged so that the interfering substance, which adheresto the removing electrodes and the filter, is formed while being joinedor linked together. 8.-13. (canceled)
 14. A method for removing aninterfering substance to be a applied to a sensor comprising a detectingunit which is provided on a substrate and which detects an objectivesubstance contained in a sample, the method comprising: allowing theinterfering substance to adhere to a filter beforehand by covering thedetecting unit with the filter which permits permeation of the objectivesubstance on one hand and which regulates permeation of the interferingsubstance contained in the sample on the other hand, and removing theinterfering substance adhered to the filter by means of a removing unitwhich removes the interfering substance, wherein: the removing unit hasat least a pair of removing electrodes which are arranged in mutualcontact with the filter or closely to the filter; and the interferingsubstance adhered to the filter is removed by means of electrolyticcleaning for the removing electrodes performed by applying a voltagebetween the removing electrodes.
 15. The method for removing theinterfering substance according to claim 14, wherein the removingelectrodes are arranged so that the interfering substance, which adheresto the removing electrodes and the filter, is formed while being joinedor linked together.